Eicosanoids
Eicosanoids are bioactive signaling lipids generated from arachidonic acid and related polyunsaturated fatty acids (PUFAs) that govern a wide range of homeostatic and inflammatory processes associated with a variety of illnesses (Dennis & Norris, 2015). One of the most well-known routes involved in inflammation is the eicosanoid pathway. Inflammatory processes are the body’s physiological response to numerous stressors such as trauma, infections, or immunological reactions. These processes are distinguished by the activation of cellular and humoral mediator systems, as well as the production of a wide range of inflammatory mediators such as interleukin-1 (IL-1) and tumor necrosis factor-alpha (TNF-α). Increased amounts of these mediators can cause changes in microvascular tone and permeability, as well as activation of eicosanoid production pathways (Homaidan, Chakroun, Haidar & El-Sabban, 2002). The availability of free AA is critical for eicosanoid production. When tissues are exposed to physiological or pathological stimuli such as growth factors, hormones, or cytokines, AA is generated from membrane phospholipids by the action of phospholipase A2 (PLA2) enzymes and can then be converted into different eicosanoids. The three principal enzymes capable of metabolizing AA are P-450 epoxygenase, cyclooxygenases (COXs), and lipoxygenases (LOXs) (Harizi, Corcuff & Gualde, 2008). Following PLA2 cleavage, the freed AA is processed by three different mechanisms: cyclooxygenase (COX), lipoxygenase (LOX), and the P450 family (CYP). The COX system produces prostaglandins (PG) and thromboxanes (TX), while the LOX system produces leukotrienes (LT), hydroxyeicosatetraenoic acids (HETE), and lipoxins (LX). Finally, the CYP pathway produces epoxyeicosatrienoic acids (EET) and heterecosatrienoic acids (HETE). Although free arachidonic acid is required for the majority of eicosanoid metabolism, it is typically kept in esterified form. Phospholipase A2 (PLA2) enzymes are essential for boosting free arachidonic acid levels for metabolism and eicosanoid production under normal physiological settings, but especially after inflammatory cell activation. PLA2 isoforms comprise various cystosolic, calcium dependent, and secretory isoforms, in addition to phospholipases A1, B, C, and D. Phospholipase activity can be influenced by calcium, phosphorylation, and agonists that bind to G-protein coupled receptors. These enzymes are generally involved in the physiological remodeling of cellular membranes, with free fatty acids being extracted via phospholipase activity and subsequently recycled with another free fatty acid. Nonetheless, decreases in the cell’s ability to sustain normal metabolic function, as well as the resulting drop in ATP levels, might result in the failure to recycle membrane phospholipids. Modification of membrane phospholipids is likely to affect a variety of cellular processes, including the capacity to accumulate excitotoxic amino acids. It was discovered in this study that selective phospholipase inhibitors limit the release of free fatty acids from in vivo rat brain. Following this inhibition, the severity of cortical damage after focal ischemia, forebrain ischemia, and cerebral trauma is reduced. Infarct volumes were similarly shown to be smaller in mice with PLA2 deletion (Phillis & O’Regan, 2003). Further research is needed to completely understand the role of Eicosanoids in events following SAH.